Annual Review of Pathology-Mechanisms of Disease最新文献_第2页

Zonation, Zonation, Zonation: The Real Estate of the Liver 分区，分区，分区：肝脏的房地产

IF 36.2 1区医学

Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-10-13 DOI: 10.1146/annurev-pathmechdis-042624-091820

Tyler M. Yasaka, Chang Kyung Kim, Vik Meadows, Satdarshan P. Monga

{"title":"Zonation, Zonation, Zonation: The Real Estate of the Liver","authors":"Tyler M. Yasaka, Chang Kyung Kim, Vik Meadows, Satdarshan P. Monga","doi":"10.1146/annurev-pathmechdis-042624-091820","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-042624-091820","url":null,"abstract":"The liver serves as a central hub for a diverse set of functions including metabolic homeostasis, detoxification, and protein synthesis. While appearing homogeneous, hepatocytes, the major workhorse in the liver, demonstrate spatial identity within the lobule, which in turn dictates gene and protein expression and, eventually, function. Presenting as an axis from the portal triad to the central vein, this organization has been conventionally referred to as metabolic zonation. In recent years, the heterogeneity in expression and function is now understood to extend well beyond hepatocytes and metabolism to include nonparenchymal cells and diverse functions. Although the lobule is conventionally divided into three zones, spatial multi-omics technologies reveal a more nuanced picture, where zonation provides a coordinate system for an eclectic but highly functional hepatic milieu. We summarize the current understanding of liver zonation as it contributes to division of labor, injury compartmentalization, and stepwise arrangement of metabolic pathways and discuss the implications of this framework for liver homeostasis, regeneration, and disease.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"7 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gasdermins, Executors of Pyroptosis: A Decade in Perspective. Gasdermins，焦亡的执行者：十年的观点。

IF 36.2 1区医学

Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-10-09 DOI: 10.1146/annurev-pathmechdis-042624-121548

Bowen Zhou,Derek Abbott

引用次数: 0

Immunopathology of Glioblastoma 胶质母细胞瘤的免疫病理学

IF 36.2 1区医学

Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-10-08 DOI: 10.1146/annurev-pathmechdis-042524-025950

Jiabo Li, James L. Ross, Dolores Hambardzumyan, Daniel J. Brat

{"title":"Immunopathology of Glioblastoma","authors":"Jiabo Li, James L. Ross, Dolores Hambardzumyan, Daniel J. Brat","doi":"10.1146/annurev-pathmechdis-042524-025950","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-042524-025950","url":null,"abstract":"Glioblastoma (GBM), the most frequent and malignant primary brain tumor, is characterized by a highly diverse and profoundly immunosuppressive tumor microenvironment (TME) that provides an unconstrained environment for tumor progression and significantly complicates therapeutic interventions. Despite advances in immunotherapeutic approaches, such as chimeric antigen receptor T cell and immune checkpoint inhibitors, efficacy remains limited due to the complexity of the GBM TME and robust immune evasion mechanisms. In this review, we elucidate the intricate interplay among cellular components within the TME that lead to this immunosuppressive state, including tumor-associated macrophages/microglia, myeloid-derived suppressor cells, regulatory T cells, and glioma stem cells, as well as other critical elements that contribute to TME complexity, such as the severe hypoxia associated with central necrosis, the blood–brain barrier, and the extracellular matrix. This review also highlights mechanisms of immune evasion and recent immunotherapeutic approaches along with their biologic rationale, underscoring the need for integrated therapeutic strategies that both target immunosuppressive elements and enhance immune activation.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"36 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular Subtypes of Neuroendocrine Carcinoma: From Chaos to Consensus. 神经内分泌癌的分子亚型：从混乱到一致。

IF 36.2 1区医学

Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-10-08 DOI: 10.1146/annurev-pathmechdis-042524-023153

Zhanyu Wang,Nan Sun,Jie He,Esther Redin,Charles M Rudin

{"title":"Molecular Subtypes of Neuroendocrine Carcinoma: From Chaos to Consensus.","authors":"Zhanyu Wang,Nan Sun,Jie He,Esther Redin,Charles M Rudin","doi":"10.1146/annurev-pathmechdis-042524-023153","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-042524-023153","url":null,"abstract":"Neuroendocrine carcinomas (NECs) represent a notoriously aggressive family of lethal malignancies arising across diverse anatomical sites. Molecular subtyping based on key transcription factors ASCL1, NEUROD1, POU2F3, and YAP1 has significantly advanced understanding of tumor heterogeneity in small cell lung cancer (SCLC). Beyond SCLC, extrapulmonary NECs demonstrate analogous heterogeneity, similarly governed by these transcriptional determinants. Recent studies have further identified a fifth subtype driven by the lineage-specifying factor HNF4A. This review aims to propose a unified pan-NEC classification framework for consistent molecular subtyping across pulmonary, gastro-entero-pancreatic (GEP), and genitourinary systems. We delineate the distinct lineage hallmarks of the ANHPY subtypes (neuroendocrine, neuronal, GEP-like, tuft-like, and epithelial-mesenchymal transition phenotypes) and explore their connections to defining mechanisms, genetic alterations, clinicopathological features, and therapeutic vulnerabilities. This unified framework serves as a molecular roadmap for precise NEC research and management.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"62 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of Chromatin Looping Factors in Leukemia. 染色质环化因子在白血病中的作用。

IF 36.2 1区医学

Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-09-15 DOI: 10.1146/annurev-pathmechdis-051222-014420

Shira G Glushakow-Smith,Zuzana Tothova

引用次数: 0

Exploring the Complex Pathophysiology of Necrotizing Enterocolitis in Preterm Neonates. 探讨早产儿坏死性小肠结肠炎的复杂病理生理学。

IF 36.2 1区医学

Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-09-15 DOI: 10.1146/annurev-pathmechdis-070224-014223

Bo Li,Mina Yeganeh,Dorothy Lee,Sinobol Chusilp,Felicia Balsamo,Niloofar Ganji,Chen-Yi Wang,Andrea Zito,George Biouss,Agostino Pierro

{"title":"Exploring the Complex Pathophysiology of Necrotizing Enterocolitis in Preterm Neonates.","authors":"Bo Li,Mina Yeganeh,Dorothy Lee,Sinobol Chusilp,Felicia Balsamo,Niloofar Ganji,Chen-Yi Wang,Andrea Zito,George Biouss,Agostino Pierro","doi":"10.1146/annurev-pathmechdis-070224-014223","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-070224-014223","url":null,"abstract":"Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm neonates, with a mortality rate of 30-50% in advanced cases. Despite decades of research, its multifactorial pathophysiology remains incompletely understood. This review summarizes recent advances in NEC research and proposes an integrative theoretical framework for its pathogenesis. We examine key contributing factors, including intestinal vascular development, mucosal immunity, intestinal regeneration, the enteric nervous system, and the gut microbiome, highlighting how prematurity disrupts these processes and predisposes neonates to NEC. Furthermore, we propose a sequential model of NEC pathogenesis, hypothesizing that impaired intestinal microcirculation in preterm neonates compromises blood flow in response to enteral feeding, leading to localized ischemia. This initiates epithelial barrier dysfunction, exacerbates inflammatory responses, impairs intestinal regeneration, and disrupts enteric nervous system function, collectively driving NEC progression. By integrating experimental and clinical findings, we provide a comprehensive perspective on NEC initiation in preterm neonates and identify potential avenues for future research and therapeutic interventions.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"13 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clonal Hematopoiesis in Nonmalignant Disease: Functional Consequences of Mutated Immune Cells by Clonal Hematopoiesis in the Diseased Tissue. 非恶性疾病中的克隆造血：病变组织中克隆造血导致免疫细胞突变的功能后果。

IF 36.2 1区医学

Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-09-10 DOI: 10.1146/annurev-pathmechdis-111523-023442

Youngil Koh,Isak W Tengesdal,Siddhartha Jaiswal

{"title":"Clonal Hematopoiesis in Nonmalignant Disease: Functional Consequences of Mutated Immune Cells by Clonal Hematopoiesis in the Diseased Tissue.","authors":"Youngil Koh,Isak W Tengesdal,Siddhartha Jaiswal","doi":"10.1146/annurev-pathmechdis-111523-023442","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-111523-023442","url":null,"abstract":"Clonal hematopoiesis, originally identified as a precursor to hematologic malignancies, has emerged as a significant factor in various nonmalignant diseases. Recent research highlights how somatic mutations in hematopoietic stem cells lead to the expansion of circulating mutated immune cells that exert profound effects on organ function and disease progression. These mutated clones display altered inflammatory profiles and tissue-specific functional consequences, contributing to various diseases including atherosclerotic cardiovascular disease, osteoporosis, heart failure, and neurodegenerative conditions. Key mutations, particularly in genes regulating epigenetics (TET2, DNMT3A, ASXL1), splicing (SF3B1, U2AF1), and DNA damage repair (TP53, PPM1D), modify immune responses and promote chronic inflammation. Intriguingly, while clonal hematopoiesis exacerbates many inflammatory conditions, it has been linked to a protective effect in Alzheimer's disease, potentially due to enhanced microglial function. Understanding the mechanistic underpinnings of clonal hematopoiesis in nonmalignant disease may inform targeted therapeutic strategies, particularly those aimed at modulating inflammation. This review explores the gene- and organ-specific roles of clonal hematopoiesis, highlighting its implications for disease pathogenesis and potential interventions.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"45 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fibroblast Modulation of Stem Cell Lineage Infidelity and Metaplasia in Tissue Fibrosis 成纤维细胞对组织纤维化中干细胞谱系不忠和化生的调节

IF 36.2 1区医学

Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-08-21 DOI: 10.1146/annurev-pathmechdis-042624-111827

Tsukasa Kadota, Tien Peng

引用次数: 0

Unraveling Mechanisms of Genetic Risks in Metabolic Dysfunction-Associated Steatotic Liver Diseases: A Pathway to Precision Medicine. 代谢功能障碍相关脂肪变性肝病遗传风险机制的揭示：通往精准医学的途径。

IF 34.5 1区医学

Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-01-01 DOI: 10.1146/annurev-pathmechdis-111523-023430

Xiang Zhang, Kyong-Mi Chang, Jun Yu, Rohit Loomba

{"title":"Unraveling Mechanisms of Genetic Risks in Metabolic Dysfunction-Associated Steatotic Liver Diseases: A Pathway to Precision Medicine.","authors":"Xiang Zhang, Kyong-Mi Chang, Jun Yu, Rohit Loomba","doi":"10.1146/annurev-pathmechdis-111523-023430","DOIUrl":"10.1146/annurev-pathmechdis-111523-023430","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health problem, affecting ∼1 billion people. This condition is well established to have a heritable component with strong familial clustering. With the extraordinary breakthroughs in genetic research techniques coupled with their application to large-scale biobanks, the field of genetics in MASLD has expanded rapidly. In this review, we summarize evidence regarding genetic predisposition to MASLD drawn from family and twin studies. Significantly, we delve into detailed genetic variations associated with diverse pathogenic mechanisms driving MASLD. We highlight the interplay between these genetic variants and their connections with metabolic factors, the gut microbiome, and metabolites, which collectively influence MASLD progression. These discoveries are paving the way for precise medicine, including noninvasive diagnostics and therapies. The promising landscape of novel genetically informed drug targets such as RNA interference is explored. Many of these therapies are currently under clinical validation, raising hopes for more effective MASLD treatment.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"20 1","pages":"375-403"},"PeriodicalIF":34.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Roles of Cellular Neighborhoods in Hepatocellular Carcinoma Pathogenesis. 细胞邻域在肝癌发病机制中的作用。

IF 34.5 1区医学

Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-01-01 DOI: 10.1146/annurev-pathmechdis-111523-023520

Lichun Ma, Cherry Caiyi Li, Xin Wei Wang

引用次数: 0